title: Site-specific inactivation of aldose reductase by 4-hydroxynonenal.
abstract: Bovine lens aldose reductase (ALR2), which catalyzes the NADPH-dependent reduction of 4-hydroxy-2-nonenal (HNE), is readily inactivated by its own substrate in a time- and concentration-dependent manner. Both DTT and NADP+ can prevent enzyme inactivation but neither extensive dialysis nor thiol-reducing treatment were able to restore enzyme activity once inactivation had occurred. Unlike the native enzyme, S-glutathionyl-modified ALR2 is unaffected by HNE, and can be easily reverted to the native form under thiol-reducing conditions. Evidence is presented of the involvement of Cys298 in the inactivation process. Zofenoprilat, an antioxidant thiol compound, mimics the effect of GSH. The possibility is raised that enzyme thiolation may function as a protection mechanism against the irreversible modification of ALR2.
authors.affiliation: Dipartimento di Fisiologia e Biochimica, Università di Pisa, via S. Maria, Pisa, 55, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Del Corso
authors.forename: M
authors.initials: M
authors.lastname: Dal Monte
authors.forename: P G
authors.initials: PG
authors.lastname: Vilardo
authors.forename: I
authors.initials: I
authors.lastname: Cecconi
authors.forename: R
authors.initials: R
authors.lastname: Moschini
authors.forename: S
authors.initials: S
authors.lastname: Banditelli
authors.forename: M
authors.initials: M
authors.lastname: Cappiello
authors.forename: L
authors.initials: L
authors.lastname: Tsai
authors.forename: U
authors.initials: U
authors.lastname: Mura
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002216:Captopril / Q000031:analogs & derivatives / Q000494:pharmacology; D002417:Cattle; D003545:Cysteine / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D019803:Glutathione Disulfide / Q000494:pharmacology; D007908:Lens, Crystalline / Q000201:enzymology; D009249:NADP / Q000494:pharmacology
chemical_list: D000447:Aldehydes; D000975:Antioxidants; C065520:zofenoprilate; D009249:NADP; D002216:Captopril; D000449:Aldehyde Reductase; C027576:4-hydroxy-2-nonenal; D003545:Cysteine; D004229:Dithiothreitol; D019803:Glutathione Disulfide